Comparative 2D and 3D-QSAR of antifungal griseofulvin analogues

Abstract

A series of griseofulvin analogues has been examined to determine the structural requirements of antifungal activity by three-dimensional quantitative structure-activity relationship studies using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA ) methods. Evaluation of 22 compounds (training set) has established the CoMFA and CoMSIA models, which have been validated by evaluation of a set of four compounds (test set). The lowest energy conformer of the most active molecule obtained from systematic search has been used as the template structure for the alignment. In this study, the superimposition of molecules was carried out by atom-based fit (rms), multi fit and field fit. Along with steric and electronic fields, ClogP has been taken as additional descriptor to account for lipophilicity. Further, a QSAR analysis has been carried out using Tools for Structure-Activity Relationship software. For this study, various chemical descriptors such as electronic, steric, lipophilic, topological have been calculated and multiple regression carried out. The QSAR models from these three methods exhibit considerable correlative and predictive properties. The models obtained from the present study may be useful for the development of new griseofulvin analogues as potential antifungals.